Metabolic
RBC Disorders
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency)Anemia
can be caused by a metabolic
disorder that interferes with the integrity of the red blood cell membrane.
An important enzyme deficiency is the G6PD
deficiency, which is an X-linked disorder and fully expressed in the male
and in homozygous females. In heterozygous females it is expressed in a variable
fashion. There are more than 100 known mutants of this disorder,
but clinically the most important one is a drug sensitive variety that affects
approximately 10% of black males in the US and less than 10% female blacks. People
of Mediterranean origin are much less affected by this disorder. Because
the older red blood cells are affected in this disorder more than the young ones,
there is hemolysis of older RBC’s. Certain conditions that strain RBC’s as
well like fever, viral or bacterial infections and diabetic acidosis, will lead
to even more anemia by hemolysis. Certain drugs and substances can produce peroxide
and cause oxidation of hemoglobin and red blood cells, which in turn can cause
hemolysis. Simple drugs like ASA, sulfonamides, phenacetin, dapsone, vitamin K
derivatives, and even consuming fava beans will cause hemolysis in susceptible
people. Many affected people react to fentanyl, a drug that is used for anesthetic
induction, with an acute hemolysis. The anesthetist has to use different drugs
during surgery. There are enormous differences between people in the sense that
the G6PD deficiency is expressed in different degrees of severity (dependent on
gene expression). In blacks the older cell population of RBC’s is selectively
targeted by hemolysis putting a limit of less than 25% of the total RBC mass that
can be affected. In whites all of the RBC’s can be affected so that they tend
to get a much more severe hemolysis, which can be lethal in severe cases. The
degree of severity depends on the dose of the offending drug or substance and
on how much peroxide is formed by this toxic process. With severe hemolysis hemoglobinuria
and kidney failure can develop from the hemolytic process. Symptoms
A patient, who is anemic and has an acute hemolytic anemia with jaundice,
particularly in a black male, should be checked for G6PD deficiency. Chills, a
fever and pain in the back and in the stomach may accompany the anemia. Diagnosis
The reticulocytes are increased markedly during hemolysis. Heinz bodies
occur early in the illness, but are subsequently removed by the spleen. Also cells
that look like a bite was taken from the periphery (bit cells) are characteristic
of G6PD deficiency. Specific enzymes assays are available to come to the accurate
diagnosis. Treatment Treatment during a hemolysis
attack is supportive. It would be rare to require a transfusion of blood. Any
drug or substance that can be identified as having precipitated the bout of acute
hemolysis would have to be avoided from now on. No treatment is available to fix
the genetic defect.
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